There is a gray area where optimism in a research patient in early phase cancer trials crosses over to a misperception of benefit and raises ethical questions about informed consent, says Lynn A. Jansen, PhD, associate director of the Center for Ethics in Health Care at Oregon Health & Science University in Portland.

“I have served on IRBs and something we are all concerned with is ensuring patient-subjects provide a fully informed consent when they enroll in research trials,” she tells IRB Advisor. “Informed consent is about respecting people’s autonomy. If people are making decisions based on biases and errors in judgment, then there is a harm.”

Cancer patients desperate to fight the disease may perceive participation in an early-phase cancer trial as an option by which they can assume some control over the course of the disease, she explains in a recently published paper.1 These perceptions of control can in turn evoke ‘‘optimistic bias:” erroneous thinking that exaggerates the likelihood of benefit.

For example, in a Phase I cancer trial designed to test the toxicity of drugs, research subjects may be informed that participating will not benefit their health. The trial could, however, generate data that may be beneficial to future patients. Despite this relatively straightforward informed consent, some subjects in such trials manifest optimistic bias, she says.

“Even though that information is in the documents and hopefully included in the informed consent discussion between the researcher and the patient, when you interview patients they have this view that they are going to benefit from these trials,” Jansen says. “That’s the reason they are enrolling: to cure their cancer. And they have the belief that they are more likely to benefit than other people who are in the same trial. So something is happening in between the IRB approving the informed consent — which provides specific, concrete information that this trial is not designed to benefit you — and the time when the person agrees to participate and actually enrolls. There’s a disconnect.”

Beyond positive thinking

Jansen and other researchers have previously identified therapeutic optimism as a possible defect in the process of informed consent of early-phase cancer research.2 Certainly, some research subjects will reflect a positive attitude indicative of the way they cope with life, but optimistic bias suggests a failure to adequately process or appreciate relevant research information.

“Beyond the concern for autonomy there is also an issue of well-being,” she says. “We don’t know how a person who enrolls in an early phase cancer trial is going to feel at the end of that trial when it does not improve their condition — if they are thinking that it will. So there is potential harm to a person’s well-being and autonomy, and I think both of those are ethical issues.”

As a practical matter, Jansen suggests the researchers specifically ask research patients their perceptions of the benefits of the clinical trial rather than simply telling them and giving them a form to sign.

“Step one is for researchers to be aware that there is this perception of control and this optimistic bias and one is generating the other,” she says. “When they are having the conversation of informed consent, ask the question: ‘What do you think your chances are of benefiting from this trial?’ If those chances are exaggerated, then take a moment to reclarify what the chances are.”

Similarly, researchers can ask research subjects their thoughts on their degree of control of the trial outcome. “If the person says they have a high degree of control over experiencing a health benefit, then the researcher can re-educate them about the nature of the research,” Jansen says.

Psych factors

Jansen argues that these perceptions of control may trigger optimistic bias, citing a study that found that 44% of subjects in a cancer trial said that participating gave them a sense of control over their disease. They concluded that the “desire to actively do something to fight their cancer appears to motivate these participants to enroll in Phase I oncology trials.”3 Again, this sense of control was often accompanied by a belief that they would benefit personally from the trial, while many other participants would not. This is strongly indicative of the optimistic bias, she says.

“Everyone cares about informed consent, but it’s more than giving a form to a person,” she says. “There is a psychology that people bring with them in that context. Researchers and IRBs need to be aware of that psychology and once we are aware of psychological [factors] that undermine risk-benefit processing — and even just understanding the information we are providing — then we can start talking about more concrete interventions that IRBs and researchers can engage in to improve how people process the information.”

In that regard, Jansen suggests an area that holds promise to resolve the situation is “mindset” research. In other fields of study, an illusory and exaggerated sense of control has been linked to a specific mindset associated with implementation of adopted plans or goals. The “implementation mindset” occurs when a decision has been made to act. Though additional research would be needed to verify the hypothesis, Jansen says early-phase cancer trial research patients appear to manifest the implementation mindset.

Having decided to participate in an early-phase cancer trial, research subjects take action and by implementing their plan have an increased perception of control and, subsequently, optimistic bias about their health outcome, she says. Jansen theorizes that the aforementioned “disconnect” is because research subjects may not be in the implementation mindset when they first agree to the informed consent. The theory awaits more research, and Jansen is also interested in determining if optimistic bias can be found in later-stage cancer trials.

“We’ve only studied the optimistic bias in the context of early phase cancer trials,” she says. “We are looking at later-stage trials and trying to determine if the bias still exists.”

REFERENCES

  1. Jansen LA. The optimistic bias and illusions of control in clinical research. IRB: Ethics & Human Research 2016;38(2):8-14.
  2. Jansen LA. The problem with optimism in clinical trials. IRB: Ethics & Human Research 2006;28(4):13-19.
  3. Agrawal M, Grady C, Fairclough DL, et al. Patients’ decision making process regarding participation in phase 1 oncology research. Journal of Clinical Oncology 2008; 24(7):4479-4484, p. 4482.